Emissions from port operation and shipping have a significant impact on climate risk affecting the environment and human health in coastal regions (UNEP; IPCC). The port of Heraklion, located on the island of Crete over the eastern Mediterranean, plays a key role in the sustainability of Southeast Europe. Its impact on operation affects the socio-economic life and development because Heraklion is not just a tourist destination, but also a significant trade and transportation center over the eastern Mediterranean. This study investigates the impact of port operation on the air quality of Heraklion between two representative periods. The first, which is considered as the high port-activity season was conducted from 02.08.2018 to 08.08.2018, while the second one between 11.05.2018 and 16.05.2018. For the air quality measurements, a low-cost sensor is used while the recordings are initially compared and finally evaluated based on the available data of the monitoring station of the Ministry of Environment and Energy. To investigate the air quality differences between the two studied periods, the correlation analysis, the hourly evolution of pollutants, the mean differences between high and low period for gaseous pollutants and particulate matter are studied. Moreover, the effect of meteorology on air quality is investigated. The results indicate that the high season is characterized by significantly higher concentrations of pollutants compared to the other. In both seasons studied, the air pollution level increases during hours of high port-activity indicating the impact of the port-activity on air quality in Heraklion. The analysis shows that meteorology affects the air quality. In particular, strong wind speeds are associated with lower concentrations of gaseous pollutants other than ozone which is affected by atmospheric circulation. Finally, the analysis emphasizes the importance of further investigation of the impact of port operations on coastal air quality in the context of sustainable development.